Study of Out of Specification for Tisagenlecleucel

A Phase IIIb Study of the Safety and Efficacy of Tisagenlecleucel Out of Specification for Commercial Release in Patients Who Are Consistent With the Label Indication

This study will evaluate the safety of tisagenlecleucel that is out of specification( OOS) for release as commercial product. Specifically, this study will evaluate the safety of CTL019 in the patients treated within the approved label by Japan Health Authority in Part 2. Only for Part 1, in addition to safety, key efficacy of CTL019 will also be evaluated.

This is a single-arm, open-label, multicenter, interventional Phase IIIb study in pediatric/young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (pALL) and adult patients with r/r large B-cell lymphoma (LBCL) including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B cell lymphoma, and DLBCL arising from follicular lymphoma for Part 1 and and r/r ALL and r/r non-Hodgkin's lymphomas (NHL) for Part 2

Patients whose final manufactured tisagenlecleucel patient-specific batch does not meet the approved local commercial release specifications are eligible for inclusion. Each case will be individually assessed and approved by the Novartis manufacturing facility and the Novartis global medical team (including Patient Safety). Following a single infusion of CTL019, the patient will be followed for 3 months for Part 1, and 1 day for Part 2.

Key inclusion criteria:

• Signed informed consent/assent must be obtained for this study prior to participation in the study.
• Patients for whom the final manufactured tisagenlecleucel product does not meet the commercial release specifications.
• Not excluded from commercial manufacturing under the Health Authority-approved tisagenlecleucel prescribing information for their respective country/region.
• OOS material has not been deemed to pose an undue safety risk to the patient.
• Patient is suffering from a serious or life-threatening disease or condition.
• Repeat leukapheresis is not clinically appropriate per the investigator assessment.

Key exclusion criteria:

For part 1, patients meeting any of the following criteria are not eligible for inclusion in this study:

• Human immunodeficience virus (HIV) positive patients.
• Patients with active replication of Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
• Patients with primary central nervous system (CNS) lymphoma.
• History of hypersensitivity to any drugs or metabolites of similar chemical classes as tisagenlecleucel.
• Uncontrolled active infection or inflammation.
• Any medical condition identified by the investigator that may impact the assessment of the safety or efficacy outcomes in relation to study treatment.
• Pregnant or nursing (lactating) women. For part 2, exclusion criteria are not set; however, administration should be performed in accordance with the latest versions of the package insert of CTL019.